Permeability of injured and intact peripheral nerves and dorsal root ganglia

Background: Nerve injury that produces behavioral changes of allodynia and hyperalgesia in animals is associated with electrophysiologic changes in dorsal root ganglion (DRG) cells. The introduction of drugs into the DRG or the peripheral nerve that alter calcium, sodium, or potassium channel activity may be of therapeutic benefit after nerve injury. For this reason, the authors sought to determine whether drugs that do not ordinarily cross the blood-nerve barrier will enter the DRG after intravenous or regional injection and to determine whether nerve injury alters drug access to DRGs or peripheral nerves. Methods: Both intact and spinal nerve-ligated rats were injected with sodium fluorescein by intravenous, intrathecal, peri-DRG, perisciatic, and epidural routes. DRG, sciatic nerve, and spinal cord tissues were harvested and frozen, and histologic sections were analyzed quantitatively for tissue fluorescence. Results: In both intact and nerve-injured animals, fluorescein accumulated in DRGs after intravenous, peri-DRG, and epidural injection. There was accumulation in the proximal portion of the ganglion after intrathecal injection. Minimal amounts of fluorescein were found in the sciatic nerve in intact animals after intravenous or perineural injection, but substantial amounts were found in some nerve fascicles in nerve-injured animals after both intravenous and perineural injection. There was almost no fluorescein found in the spinal cord except after intrathecal administration. Conclusions: In both intact and nerve-injured animals, fluorescein accumulates freely in the DRG after intravenous, epidural, or paravertebral injection. The sciatic nerve is relatively impermeable to fluorescein, but access by either systemic or regional injection is enhanced after nerve injury.